Evaluation of concomitant treatment for Chronic Pelvic Pain Syndrome

Introduction

Chronic pelvic pain syndrome (CPPS) is one of the most common diseases in Urology and Pain is located in the pelvic area that can originate in the pelvic musculoskeletal, gastrointestinal or nervous system that lasts more than 6 months.^1,2

CPPS syndrome seems to be a multifactorial disorder and results from the interaction between dysfunction in the neurological, endocrine and immune system and psychological factors. ³ Some changes in the central nervous system could lead to perception of pain while no acute injury is detected and some changes may increase perception of nonpainful stimuli as painful called allodynia and some other may cause painful stimuli to cause more pain than expected called hyperalgesia. ⁴ Pain could became severe enough to limit functioning sexual activity and increase the risk of erectile dysfunction, with significant impact on quality of life. ⁵ Considering the complexity of it and a limited armamentarium that we can use to treat it; the trials show a modest effect and limited responders. Antibiotics, alpha-blockers, and anti-inflammatory agents should be considered alone or in combination to treat and help improve the impact that disease has on patient symptoms and quality of life. ⁶ Although, because of a lack of key targets the management of this bothersome condition is so challenging, but our current understandings suggest multimodal therapeutic strategies. ⁷

Methods

This cross-sectional study analyzed data from 96 male patients aged older than 17 and younger than 40, who were selected from affiliated hospitals of The Islamic Azad University of Medical Science (Tehran, Iran). The hospitals included Buali, Farhikhtegan, and Amiralmomenin Hospital. These patients were diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) based on the inclusion criteria specified by The National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI). The data collection period spanned from March 2022 to March 2023. Pain severity categories were determined using the results for NIH-CPSI item 4, which utilized a numerical rating scale ranging from 0 to 10 for average pain. Categories were defined as follows: mild (0–3), moderate (4–6), and severe (7–10). Additionally, the CPSI pain domain, ranging from 0 to 21, categorized pain severity as mild (0–7), moderate (8–13), and severe (14–21). ⁸

Patients included in the study had been suffering from the disease for at least 6 months prior to the initiation of the study. Exclusion criteria for participation in the study included intolerance to the prescribed drugs and expressed displeasure with participating in the study. All participants provided written informed consent, and the study protocol was reviewed and approved by the ethical committee for biomedical research at Islamic Azad University of Medical Science by the number IR.IAU.TMU.REC.1401.006.

In this study, there was only one patient group, and no placebo group was included. The patients were treated simultaneously with three drugs: tamsulosin 0.04 mg per day, levofloxacin 500 mg per day, and celecoxib with a daily dosage of 200 mg for 1 month. After the treatment period, the response to treatment, as pain relief by a Visual Analog Scale (VAS) score of 0 (no), 1–3 (mild), 4–6 (moderate), 7–9 (severe), and 10 (very severe) was used to measure the patients’ pain, was evaluated considering factors such as age, weight, underlying disease, smoking status, BMI, family history of prostatitis, and education level. Additionally, the researcher recorded a demographic profile using prepared data collection forms. Statistical analysis was performed using SPSS version 20.0 (SPSS Inc., Chicago, IL).

Data were shown as mean ± SD and number (percent). A p-value less than 0.05 was considered a significant threshold.

The data was entered into the SPSS software for analysis. To control for potential confounding variables, including age, BMI, and smoking status, we performed a multivariate analysis. Descriptive statistics such as frequency and proportion were used for qualitative data, while measures such as mean and standard deviation were employed for quantitative data. To examine the relationship between qualitative variables, the Chi-square test was utilized. For assessing the relationship between mean values of quantitative data across qualitative groups, the independent t-test was employed if the normality assumption was met; otherwise, the Mann-Whitney U test was used. In all cases, a significance level of less than 0.05 was considered.

Results

Pain relief was achieved in 41 patients, representing 42.7% of the study population. The mean age in patients with pain relief was 28.34 ± 1.046 and in patients without pain relief was 31.89 ± 0.843 years (p = 0.009). The mean weight was 84.92 ± 2.56 kg in patients with pain relief and 79.65 ± 1.94 kg in patients without pain relief (p = 0.105). The mean BMI in patients with pain relief was 24.36 ± 0.69 and in patients without pain relief was 25.07 ± 0.45 kg/m² (p = 0.323; Table 1). There was a significant relationship between the underlying disease and reduction of postoperative pain (p < 0.001) and smoking and reduction of postoperative pain (p < 0.001) and family history of prostatitis and reduction of postoperative pain (p = 0.032). Minor adverse effects were observed in a small subset of patients, including mild headaches and occasional nausea. These side effects were transient and did not impact the overall efficacy of the treatment. No significant relationship was found between education and reduction of pain after treatment (p = 0.82). Weight gain reduced the chances of reducing pain in patients after treatment (OR = 0.303, CI = 95%). Increased BMI decreased the chances of reducing pain in patients after treatment (OR = 0.476, CI = 95%). Smoking reduced the chances of reducing pain in patients after treatment (OR = 0.801, CI = 95%) (Table 2). Considering the patient’s health condition, we observed no important adverse effect.

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Table 1.

Demographic data.

Variables	Mean	SEM	SD	Lowest	Highest	Mean of pain relief	Non-responders	p-Value
Age	30.38	0.679	6.649	17	40	28.34 ± 1.04	31.89 ± 0.84	0.009
Weight	81.9	1.57	15.43	55	108	84.92 ± 2.56	79.65 ± 1.94	0.105
BMI	24.77	0.393	3.85	18.7	31	24.36 ± 0.69	25.07 ± 0.45	0.323

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Table 2.

Logistic regression analysis: Factors affecting pain relief in chronic pelvic pain syndrome patients.

Variable	Odds Ratio (OR)	95% Confidence interval (CI)	p-Value
Age	0.976	0.915–1.043	0.564
Weight (kg)	1.256	0.987–1.601	0.072
BMI (kg/m2)	0.891	0.741–1.072	0.189
Underlying disease	0.359	0.195–0.661	< 0.001
Smoking status	0.648	0.442–0.949	0.027
Family history	1.185	0.819–1.712	0.358

Discussion

Pain experienced in the pelvis is a common symptom of CP/CPPS. The etiology of this pain is not clear yet. ² Pain severity seems to have more impact on the patient’s quality of life than urinary symptoms. ⁹ Regarding previous studies that evaluated the efficacy of various treatments, there is no consensus on the best treatment for them. A comprehensive study to evaluate the response to concomitant therapy was not available. Although separate studies have been conducted on individual drugs and in comparison, on placebo, which support our findings, response to treatment with concomitant use of tamsulosin, levofloxacin, and celecoxib in chronic pelvic pain syndrome in men has acceptable conclusion for reliving the patient’s pain.

Regarding pervious experiences, tamsulosin was superior to placebo for symptomatic relief of moderate to severe CP/CPPS as measured by the NIH-CPSI that contains pain also and no severe side effects were seen.^2,10 The pain may be related with substance P(SP)released in the spinal cord with stimulation of pain receptors in the prostate, and may be attenuated by adrenergic antagonists. SP probably plays an important role in mediating nociceptive processing from the prostate. Tamsulosin can attenuate nociception-induced SP upregulation within the spinal cord. ¹¹ In another article, traditionally, experts in the subject of prostatitis have recommended that antibiotics should only be used for culture proved bacterial prostatitis. ¹²

A placebo-controlled study showed that after 6 weeks treatment with levofloxacin in patients diagnosed with CP/CPPS resulted in improvement in symptoms that was not significantly different from that with placebo at the end of therapy or follow-up, as the writers recommended a greater study. ¹³ A combination treatment with alpha-blocker and levofloxacin can reduce the CPSI score. ¹⁴ According to a study in 2004 treatment with celecoxib was effective and no serious side effect was detected and the dosage of 200 mg twice a day had more efficacy in comparison with 200 mg per day. ¹⁵ in another study related to celecoxib therapy in patients results showed significant improvement in symptoms that were limited to the duration of therapy in difficult chronic pelvic pain compared to the placebo. ¹⁶ Our study contributes to the existing literature by evaluating the efficacy of concomitant therapy with tamsulosin, levofloxacin, and celecoxib in alleviating CPPS symptoms. By considering the pharmacological mechanisms of each medication and their potential synergistic effects, we provide insights into the rationale behind the observed improvement in patient symptoms. However, these findings are limited by the short duration of observation, as the study only assessed outcomes within a 30-day treatment period, which precludes conclusions regarding the long-term sustainability of the observed benefits. Furthermore, the absence of a control or placebo group restricts the ability to isolate the specific effects of the combination treatment from potential placebo responses. The relatively small sample size and non-randomized design also limit the generalizability and causal interpretability of the results. To address these limitations, future studies with larger, randomized controlled samples, extended follow-up periods, and a control group are recommended. Such studies would provide more robust evidence on the long-term efficacy and applicability of this combination therapy relative to placebo effects or alternative treatments.

Conclusions

The findings of our research revealed that administering tamsulosin, levofloxacin, and celecoxib simultaneously in chronic pelvic pain syndrome and chronic prostatitis patients could have satisfactory results in alleviating their pain and can be pivotal in improving patient’s lives and enhancing their overall quality of life.